LP-BM5 murine leukemia virus, a derivative of Duplan-Laterjet virus, contains a mixture of replication-competent B-tropic ecotropic and mink cell focus-inducing (MCF) viruses and a defective genome that is characterized by combined biological and molecular techniques as the proximal cause of a syndrome, murine AIDS (MAIDS), manifested by lymphoproliferation and immunodeficiency. The ecotropic and 4.9kb defective genome were molecularly cloned and shown, in combination, to induce changes characteristic of MAIDS. Sequence analyses of the 4.9kb defective genome and the LTR and gag gene of the replication competent B-tropic ecotropic virus demonstrated that the defective virus was most likely derived by an initial recombination between the ecotropic virus and endogenous MCF-like sequences followed by deletion and mutation. The most highly conserved region of the 4.9kb virus in relation to the ecotropic parent is in gag with the aminoterminal portion of p12 being the most divergent. A 100bp probe from the defective p12 region was generated. In sensitive C57BL/6 mice the defective virus genome was detected in tissues within 2 weeks of infection but was absent from tissues of the MAIDS resistant strain, A/J, 12 weeks after infection. B cell lineage tumors from mice with MAIDS contained an expressed BM5 defective genome, and clonal integrations of this genome were variably associated with clonal expansions of B cells in infected mice. Protein p12 gag generated in E. coli induced high levels of antibodies in both susceptible and resistant mice but failed to induce a protective immune response.